Effect of Zuoguiwan on Wnt/β-catenin Signaling Pathway in Ovariectomized Osteoporosis Model Rats
10.13422/j.cnki.syfjx.20210539
- VernacularTitle:左归丸对去势骨质疏松模型大鼠Wnt/β-catenin信号通路的影响
- Author:
Yao-yang LI
1
;
Li-zhi SHANG
1
;
He-long SUN
1
;
Meng-di MAO
1
;
Hong-hao YAN
1
;
Chun-yu ZHOU
1
;
Guang-yuan ZHANG
1
;
Zhi-rui SUN
1
;
Zhen-yang WANG
1
Author Information
1. Henan University of Chinese Medicine， Zhengzhou 450046，China
- Publication Type:Research Article
- Keywords:
Zuoguiwan;
postmenopausal osteoporosis（PMOP）;
Wnt/β-catenin signaling pathway;
glycogen synthase kinase-3β（GSK-3β）;
low density lipoprotein receptor related protein 5（LRP5）;
bone metabolism
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2021;27(6):15-22
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe the effect of Zuoguiwan on bone metabolism and Wnt/β-catenin signaling pathway in ovariectomized osteoporotic rats model， and to explore the molecular biological mechanism of Zuoguiwan in the prevention and treatment of osteoporosis. Method:The rat model of postmenopausal osteoporosis was established by bilateral ovariectomy， 60 female SD rats were randomly divided into sham operation group， model group， positive group （estradiol valerate tablet 0.05 mg·kg-1·d-1） and low， middle and high dose groups of Zuoguiwan （5.5，11，22 g·kg-1·d-1）.After successful establishment of the model in the 13th week， intragastric administration （ig） was given once a day for a total of 12 weeks. After administration， the histomorphological changes of femur in rats were observed by hematoxylin-eosin （HE） staining， the bone mineral density （BMD） and bone mineral content（BMC） of femur were measured by dual energy X-ray apparatus， and the biomechanical properties of bone were measured by MTS Acumen3 biomechanical testing system. The contents of bone alkaline phosphatase （BALP）， bone glaprotein（BGP），estradiol （E2） ，and tartrate-resistant acid phosphatase （TRAP）， type Ⅰ procollagen N-terminal propeptide （PINP） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the protein level of Wnt2，β-catenin，low density lipoprotein related receptor protein 5 （LRP5） and the phosphorylation level of glycogen synthase kinase-3β（GSK-3β） in rat tibia. Result:Compared with sham operation group， the maximum load and stiffness of BMD，BMC， in the model group decreased significantly（P<0.01）， the contents of E2 and PINP in serum decreased significantly（P<0.01）， the content of BALP，BGP，TRAP increased significantly（P<0.01）， the expression levels of Wnt2，p-GSK-3β Ser9，LRP5 and β-catenin protein in bone tissue decreased significantly（P<0.01）， the trabecula of femur became thinner and thinner， the number of bone trabeculae decreased. Compared with model group， the maximum load and stiffness of BMD，BMC， in estradiol group and Zuoguiwan group were significantly increased （P<0.05，P<0.01）， the contents of serum E2 and PINP were significantly increased （P<0.05，P<0.01）， the content of BALP，BGP，TRAP was significantly decreased （P<0.01）， and the expression level of Wnt2，p-GSK-3β Ser9，LRP5， β-catenin protein in bone tissue was significantly increased （P<0.05，P<0.01） ， the trabeculae of femur became thicker， the number increased， the structure was basically clear. Conclusion:Zuoguiwan has a certain preventive and therapeutic effect on osteoporosis in ovariectomized rats， and its mechanism may be related to increasing the level of estrogen， activating Wnt/β-catenin signaling pathway， up-regulating the expression of Wnt2 and LRP5 protein， inhibiting the activity of GSK-3β， reducing the degradation of β-catenin， coordinating the dynamic coupling balance between bone formation and bone resorption， correcting the disorder of bone metabolism and improving bone morphology.
